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首页> 外文期刊>Journal of Neurophysiology >The IGF-derived tripeptide Gly-Pro-Glu is a weak NMDA receptor agonist
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The IGF-derived tripeptide Gly-Pro-Glu is a weak NMDA receptor agonist

机译：IGF衍生的三肽Gly-Pro-Glu是一种弱NMDA受体激动剂

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Glutamate acts as the universal agonist at ionotropic glutamate receptors in part because of its high degree of conformational flexibility. Other amino acids and small peptides, however, can activate N-methyl-D-aspartate (NMDA) receptors, albeit usually with lower affinity and efficacy. Here, we examined the action of glycine-proline-glutamate (GPE), a naturally occurring tripeptide formed in the brain following cleavage of IGF-I. GPE is thought to have biological activity in the brain, but its mechanism of action remains unclear. With its flanking glutamate and glycine residues, GPE could bind to either the agonist or coagonist sites on NMDA receptors, however, this has not been directly tested. Using whole cell patch-clamp recordings in combination with rapid solution exchange, we examined both steady-state currents induced by GPE as well as the effects of GPE on synaptically evoked currents. High concentrations of GPE evoked inward currents, which were blocked either by NMDA receptor competitive antagonists or the voltage-dependent channel blocker Mg2+. GPE also produced a slight attenuation in the NMDA- and ?amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-mediated excitatory postsynaptic currents without altering the paired-pulse ratio. Our results suggest that GPE can activate NMDA receptors but at concentrations well above the expected concentration of GPE in the brain. Therefore, it is unlikely that endogenous GPE interacts with glutamate receptors under normal conditions.
机译：谷氨酸盐是离子型谷氨酸盐受体的通用激动剂，部分原因是其高度的构象柔韧性。但是，其他氨基酸和小肽可以激活N-甲基-D-天冬氨酸（NMDA）受体，尽管通常具有较低的亲和力和功效。在这里，我们检查了甘氨酸-脯氨酸-谷氨酸（GPE）的作用，GPE是IGF-I裂解后在大脑中形成的天然三肽。 GPE被认为在大脑中具有生物活性，但其作用机理仍不清楚。 GPE带有侧翼的谷氨酸和甘氨酸残基，可以与NMDA受体上的激动剂或激动剂位点结合，但是，尚未对此进行直接测试。使用全细胞膜片钳记录结合快速溶液交换，我们检查了GPE诱导的稳态电流以及GPE对突触诱发电流的影响。高浓度的GPE引起内向电流，该电流被NMDA受体竞争性拮抗剂或电压依赖性通道阻断剂Mg2 +阻断。 GPE还在NMDA和？氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）介导的兴奋性突触后电流中产生了轻微衰减，而没有改变配对脉冲比率。我们的结果表明，GPE可以激活NMDA受体，但浓度远高于大脑中GPE的预期浓度。因此，内源性GPE在正常条件下不可能与谷氨酸受体相互作用。

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